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Combination therapies for cancerRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, LymphokineCombination therapies for cancer description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070036748, Combination therapies for cancer. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of U.S. application Ser. No. 10/117,442, filed Apr. 5, 2002, which claims priority to U.S. Provisional Application No. 60/282,040, filed Apr. 6, 2001, and is also a continuation-in-part of U.S. application Ser. No. 10/795,090, filed Mar. 5, 2004, which claims priority to U.S. Provisional Application No. 60/452,489, filed Mar. 6, 2003. The entire texts of the above-referenced disclosures are hereby incorporated by reference. INTRODUCTION [0002] Therapy for cancer has largely involved the use of chemotherapy, in which highly toxic chemicals are given to the patient, and/or radiotherapy, in which toxic doses of radiation are administered. Chemotherapeutics that have been used successfully to combat certain cancers are frequently ineffective against other cancers, or are effective only at doses that are so high as to cause unacceptable toxicity. Although cancer chemotherapy has advanced dramatically in recent years, very few chemotherapeutic agents are curative in human cancer treatment when delivered alone. First, any single agent may only target a subset of the total population of malignant cells present, leaving a subpopulation of cancerous cells to continue growing. Second, cells can develop resistance upon prolonged exposure to a drug. Most chemotherapeutic agents must be delivered in combination with other agents to achieve curative effects. [0003] Another approach to treating cancer involves gene therapy. Gene therapy involves the transfer of a foreign polynucleotide into a cancer cell, often a polynucleotide encoding a polypeptide that is a tumor suppressor or inducer of apoptosis, under conditions suitable for expression of the therapeutic polypeptide. Once expressed, the polypeptide confers a beneficial effect on the tumor cell by either slowing its growth, inhibiting its metastatic potential, or inducing apoptosis. However, the clinical effectiveness of cancer gene therapy has been limited by the lack of control of therapeutic gene expression within the tumor and selective targeting of the vector to the tumor. [0004] Combination therapies, which employ two or more agents with differing mechanisms of action and differing toxicities, have been useful for circumventing drug resistance and increasing the target cell population. In addition, certain combinations of agents may be synergistic; in other words, their combined effect is greater than predicted based on their individual activities. Thus, combining different agents can be a powerful strategy for treating cancer. However, combination therapies do not consistently provide the desired therapeutic effect and may contribute to multi-drug resistance. In addition, antagonistic or biochemical interactions between the different therapies may lead to a reduced effectiveness and/or increased cytotoxicity for the combination than for either treatment alone. SUMMARY [0005] The present invention relates to transcriptional targeting, i.e., method of delivering a construct encoding a therapeutic polypeptide in conjunction with a chemotherapeutic agent to a subject, wherein the chemotherapeutic agent induces expression of the polypeptide. Such methods allow for the targeted expression of a therapeutic polypeptide that is directly or indirectly toxic to neoplastic and/or malignant cells, thereby avoiding toxicity that may be associated with systemic administration of the polypeptide. In addition, the combined treatment effect of the therapeutic polypeptide with chemotherapy may enhance the therapeutic response of neoplastic and/or malignant cells or a tumor to a greater degree than treatment with either therapy alone. [0006] Moreover, transcriptional targeting methods employing co-administration of a construct comprising a promoter operably linked to a polynucleotide encoding a therapeutic polypeptide and a chemotherapeutic agent are useful when it is possible to infuse or directly inject gross tumors, even in the presence of micrometastases, since the construct/chemotherapeutic agent combination is effective against gross tumor and micrometastatic disease. [0007] In one embodiment, the invention provides methods of inducing expression of a polypeptide in a cell, comprising concomitantly contacting the cells with a construct comprising an Egr-1 promoter operably linked to a polynucleotide encoding the polypeptide, and at least one chemotherapeutic agent, wherein the chemotherapeutic agent induces expression of the polypeptide. [0008] In another embodiment, the invention provides a method of inhibiting a neoplastic cell. The method comprises concomitantly contacting the cell with: a) a construct comprising an Egr-1 promoter operably linked to a polynucleotide encoding TNF-.alpha.; and b) a chemotherapeutic agent. [0009] In a further embodiment, the present invention provides methods of inhibiting or reducing the growth of a tumor in a subject, comprising co-administering to the subject: a) a construct comprising an Egr-1 promoter operably linked to a polynucleotide encoding TNF-.alpha.; and b) a chemotherapeutic agent capable of inducing expression of the TNF-.alpha. from the Egr-1 promoter. [0010] In another embodiment, the present invention provides methods of enhancing the antiproliferative effect of chemotherapy in a subject, comprising co-administering to the subject therapeutically effective amounts of a construct comprising a promoter operably linked to a polynucleotide encoding TNF-.alpha. and a chemotherapeutic agent, wherein the expression of TNF-.alpha. enhances the antiproliferative effect of the chemotherapy. [0011] Other advantages and a fuller appreciation of specific adaptations, compositional variations, and physical attributes of the invention will be gained upon an examination of the following detailed description of exemplary embodiments, taken in conjunction with the figures. BRIEF DESCRIPTION OF THE DRAWINGS [0012] FIG. 1 is a schematic diagram of an adenoviral vector comprising an Egr-1 promoter operably linked to a polynucleotide encoding TNF-.alpha. (referred to herein below as "Ad.Egr.TNF"). [0013] FIG. 2 is a graph comparing changes in fractional tumor volumes over time between untreated cells (UTC), and cells contacted with Ad.Egr.TNF, with and without cisplatin. [0014] FIG. 3 is a graph comparing levels of TNF-.alpha. expression in UTC, and cells contacted with Ad.Egr.TNF, with and without cisplatin. [0015] FIG. 4 is a graph comparing levels of TNF-.alpha. induction over time in cells contacted with Ad.Egr.TNF, with and without cisplatin. [0016] FIG. 5 is a graph comparing the response of Seg-1 cells to varying doses of cisplatin, with and without Ad.Egr.TNF. [0017] FIGS. 6A & 6B depict levels of in vitro TNF-.alpha. production by Ad.Egr.TNF-infected Seg-1 cells (6A) and PROb cells (6B) exposed to IR, cisplatin, or both, at 24, 48 and 72 hours. [0018] FIGS. 7A & 7B depict in vitro responses to radio- and chemo-induction of luciferase reporter constructs comprising luciferase reporter plasmid constructs pGL3, pGL3 660 or pGL3 425 in Seg-1 cells (7A) and PROb cells (7B). [0019] FIGS. 8A & 8B depict in vivo levels of intratumoral TNF-.alpha. produced by Seg-1 cells (8A) and PROb xenographs (8B) following treatment with Ad.Egr.TNF, with and without cisplatin. [0020] FIGS. 9A & 9B depict in vivo regrowth studies by measuring the volume of xenografts injected with a null construct (Ad.Null) and Ad.Egr.TNF, with or without cisplatin. Continue reading about Combination therapies for cancer... Full patent description for Combination therapies for cancer Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Combination therapies for cancer patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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